A Nature-Inspired Diels-Alder Reaction Facilitates Construction of the Bicyclo[2.2.2]octane Core of Andibenin B

A rapid synthesis of the bicyclo[2.2.2]octane core of andibenin B via a nature-inspired intramolecular [4+2] cycloaddition is described. This cycloaddition permits the construction of a sterically congested bicycle and simultaneously establishes three new all-carbon quaternary stereogenic centers in a highly efficient fashion.     

Imaging magnetically labeled cells with magnetomotive optical coherence tomography

We introduce a novel contrast mechanism for optical coherence tomography (OCT) whereby the optical scattering of magnetically labeled cells is modified by means of an externally applied magnetic field. This modification is made through the addition of a small electromagnet to the imaging arm of a conventional OCT interferometer. We measure the magnetomotive OCT signal by differencing pairs of axial scans (A-scans) acquired with the magnetic field on and off. Magnetomotive contrast is demonstrated in bulk three-dimensional cell scaffolds containing macrophages labeled with microparticles of iron oxide, demonstrating magnetic-specific contrast over a dynamic range of 30 dB.     

Participation of Alkoxy Groups in Reactions of Acetals: Violation of the Reactivity/Selectivity Principle in a Curtin–Hammett Kinetic Scenario

Nucleophilic substitution reactions of acetals having benzyloxy groups four carbon atoms away can be highly diastereoselective. The selectivity in several cases increased as the reactivity of the nucleophile increased, in violation of the reactivity/selectivity principle. The increase in selectivity with reactivity suggests that multiple conformational isomers of reactive intermediates can give rise to the products.     

Molecular modeling based approach to potent P2-P4 macrocyclic inhibitors of hepatitis C NS3/4A protease

Molecular modeling of inhibitor bound full length HCV NS3/4A protease structures proved to be a valuable tool in the design of a new series of potent NS3 protease inhibitors. Optimization of initial compounds provided 25a. The in vitro activity and selectivity as well as the rat pharmacokinetic profile of 25a compare favorably with the data for other NS3/4A protease inhibitors currently in clinical development for the treatment of HCV.     

Drug-delivery strategies by using template-synthesized nanotubes

Encapsulating drugs within hollow nanotubes offers several advantages, including protection from degradation, the possibility of targeting desired locations, and drug release only under specific conditions. Template synthesis utilizes porous membranes prepared from alumina, polycarbonate, or other materials that can be dissolved under specific conditions. The method allows for great control over the lengths and diameters of nanotubes; moreover, tubes can be constructed from a wide variety of tube materials including proteins, DNA, silica, carbon, and chitosan. A number of capping strategies have been developed to seal payloads within nanotubes. Combining these advances with the ability to target and internalize nanotubes into living cells will allow these assemblies to move into the next phase of development, in vivo experiments.     

Effect of aspect ratio and deformability on nanoparticle extravasation through nanopores

We describe the fabrication of filamentous hydrogel nanoparticles using a unique soft lithography based particle molding process referred to as PRINT (particle replication in nonwetting templates). The nanoparticles possess a constant width of 80 nm, and we varied their lengths ranging from 180 to 5000 nm. In addition to varying the aspect ratio of the particles, the deformability of the particles was tuned by varying the cross-link density within the particle matrix. Size characteristics such as hydrodynamic diameter and persistence length of the particles were analyzed using dynamic light scattering and electron microscopy techniques, respectively, while particle deformability was assessed by atomic force microscopy. Additionally, the ability of the particles to pass through membranes containing 0.2 μm pores was assessed by means of a simple filtration technique, and particle recovery was determined using fluorescence spectroscopy. The results show that particle recovery is mostly independent of aspect ratio at all cross-linker concentrations utilized, with the exception of 96 wt % PEG diacrylate 80 × 5000 nm particles, which showed the lowest percent recovery.     

Fibrils and nanotubes assembled from a modified amyloid-β peptide fragment differ in the packing of the same β-sheet building blocks

The peptide AAKLVFF assembles into fibrils in water and nanotubes in methanol. Solid-state NMR data are consistent with fibrils constructed from β-sheet bilayers and nanotubes bounded by a wall of offset β-sheet monolayers. Remarkably distinct morphologies are thus traced to subtle differences in the arrangement of the same fundamental building blocks.     

Investigating teachers’ appraisal of unexpected moments and underlying values: an exploratory case in the context of changing mathematics classroom discourse

This article provides an exploratory case study that examines what one teacher indicated as unexpected as she worked to become more purposeful about her classroom discourse practices. We found that she highlighted three areas as being unexpected: (1) aspects of lesson enactment; (2) characteristics of student learning and (3) her own intentionality or purposefulness. We interpret these instances through the lens of the systemic functional linguistics (SFL) appraisal framework in order to understand how she evaluates the instances she highlights and connect these instances to the literature on values in the teaching and learning of mathematics.     

Wave-Mean Flow Interactions in Thermally Stratified Poiseuille Flow

We consider nonlinear wave motions in thermally stratified Poiseuille flow. Attention is focused on short wavelength wave modes for which the neutral Reynolds number scales as the square of the wave number. The nonlinear evolution of a single monochromatic wave is governed by a first harmonic/mean-flow interaction theory in which the wave-induced mean flow is comparable in size to the wave component of the flow. An integrodifferential equation is derived which governs the normal variation of the wave amplitude. This equation admits finite-amplitude solutions which bifurcate supercritically from the linear neutral point(s).